Hallucinogens

LSD
- Found it from a fungus
- Flashbacks: gets absorbed in fat deposited in the body, and the fat deposited will
release it days or weeks later so that is what flashbacks are
o Concern because it is uncontrollable
o And builds up tolerance quickly and cross tolerance
- No documented overdoses
- It was assumed a long time ago that hallucinogens that are only serotonin, but now
know that dopamine and glutamate are involved

Lieberman: clozapine and haloperidol on ketamine-induced brain metabolic activation

- Comparing clozapine (only working in the cortex – get only the good stuff and not
parkinsonian behavior) and haloperidol (get parkinsonian behavior)
- Showed that ketamine was working on the glutamate system
- Created the glutamernergic theory of schizophrenia

Seeman
- Understand that there are 2 diff hypothesis of psychosis and schizophrenia:
hyperdopmaine and hypoglutamate
- So what is dopamine’s contribution to PCP, LSD and ketamine
- All drugs work through the same mechanism and work on the dopamine system
- Paper basically says that Lieberman wrong

Lodge
- Ketamine and phencyclidine
o Discovered that ketamine was the world’s best antidepressant because SSRIs
take too long like 2-3 weeks to work
o Ketamine is a fast-acting antidepressant
o Talked about glutaminergic mechanisms

Ketamine of the flow of time in healthy individuals

- How specific are ketamines effect on time perception (so is ketamine specific enough in
dopamine system to only effect the clock speed when given?)
- Ketamine induced selective impairments in timing

Effects of microdose LSD on time perception

- Have to look at superseconds and subseconds for different ranges
- Says you need to use a double-blind procedure controlled trials
- Looks at consciousness
- Hoping to not induce hallucinations
 - Looking at older subjects because he knows that older people have lower levels of
dopamine (vulnerable) and youll get a bigger effect than in a younger person with more
dopamine

Ketamine at a Dose that Disrupts Motor Behavior

- Given enough of this so that it has motor control
- Latent inhibition: conditioning task: if you repeatedly present a CS before and then you
try to make them learn something else, it makes them hard to make the new association
- 1st find the dose that causes motor disruption
- And then look at latent inhibition and look at the brain
o Ketamine is enhancing the prefrontal cortex efficacy
- Have glutamate release in the nucleus accumbens
- Show that both dopamine and glutamate are affected (the balance between the two)